Comparative Analysis of Gastrointestinal Microbiota Between Normal and Caudal-Related Homeobox 2 (Cdx2) Transgenic Mice

BACKGROUND/AIMS: Caudal-related homeobox 2 (Cdx2) is expressed in the human intestinal metaplastic mucosa and induces intestinal metaplastic mucosa in the Cdx2 transgenic mouse stomach. Atrophic gastritis and intestinal metaplasia commonly lead to gastric achlorhydria, which predisposes the stomach to bacterial overgrowth. In the present study, we determined the differences in gut microbiota between normal and Cdx2 transgenic mice, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). METHODS: Twelve normal (control) and 12 Cdx2 transgenic mice were sacrificed, and the gastric, jejunal, ileac, cecal and colonic mucosa, and feces were collected. To quantitate bacterial microbiota, we used real-time qRTPCR with 16S rRNA gene-targeted, species-specific primers. RESULTS: The total numbers of bacteria in the gastric, jejunal, ileac, cecal, and colonic mucosa of the Cdx2 transgenic mice were significantly higher than those of the normal mice. The Bacteroides fragilis group and also Prevotella were not detected in the stomach of the normal mice, although they were detected in the Cdx2 transgenic mice. Moreover, the Clostridium coccoides group, Clostridium leptum subgroup, Bacteroides fragilis group, and Prevotella were not detected in the jejunum or ileum of the normal mice, although they were detected in the Cdx2 transgenic mice. The fecal microbiota of the normal mice was similar to that of the Cdx2 transgenic mice. CONCLUSIONS: Our results showed the differences in composition of gut microbiota between normal and Cdx2 transgenic mice, which may be caused by the development of gastric achlorhydria and intestinal metaplasia in Cdx2 transgenic mice.

SOX9 Is Highly Expressed in Nonampullary Duodenal Adenoma and Adenocarcinoma in Humans

BACKGROUND/AIMS: SOX9 is a marker for stem cells in the intestine, and overexpression of SOX9 is found in gastric and colon cancer; however, the expression of SOX9 in nonampullary duodenal adenoma and adenocarcinoma has not yet been evaluated. This study aimed to investigate SOX9 expression in nonampullary duodenal adenoma and adenocarcinoma by immunohistochemistry. METHODS: We evaluated SOX9 expression in 43 clinical samples (nonampullary duodenal adenoma in 22 lesions and nonampullary duodenal adenocarcinoma in 21 lesions) resected under endoscopic mucosal resection or endoscopic submucosal dissection. RESULTS: SOX9 was expressed in part of the base of the normal duodenal mucosa surrounding adenomas and adenocarcinomas. In contrast, SOX9-positive cells were found in more than half of the crypts from the bottom part of the crypt in all of the 43 samples. Moreover, in 15 adenoma samples (68.2%) and 19 carcinoma samples (90.5%), SOX9 was expressed in more than three-quarters of the crypts from the bottom part of the crypt. CONCLUSIONS: SOX9 is overexpressed in nonampullary duodenal adenoma and adenocarcinoma in humans.

Asian Consensus Report on Functional Dyspepsia

BACKGROUND/AIMS: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared to the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. METHODS: Consensus team members were selected from Asian experts and consensus development was carried out using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using keypad voting system. A grade of evidence and a strength of recommendation were applied to each statement according to the method of the GRADE Working Group. RESULTS: Twenty-nine consensus statements were finalized, including 7 for definition and diagnosis, 5 for epidemiology, 9 for pathophysiology and 8 for management. Algorithms for diagnosis and management of functional dyspepsia were added. CONCLUSIONS: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.

Should We Still Subcategorize Helicobacter pylori-Associated Dyspepsia as Functional Disease?

Functional dyspepsia is a group of disorders featuring symptoms believed to be derived from the stomach and duodenum such as upper abdominal discomfort, pain, postprandial fullness and early satiety. A key diagnostic requisite is the absence of organic, metabolic, or systemic disorders to explain "dyspeptic symptoms." Therefore, when peptic ulcer diseases (including scars), erosive esophagitis and upper gastrointestinal malignancies are found at endoscopic examinations, the diagnosis of functional dyspepsia is excluded. One notable exception, however, is Helicobacter pylori infection. According to the Rome III definition, H. pylori infection is included in functional dyspepsia. This is an obvious deviation from the diagnostic principle of functional dyspepsia, since H. pylori infection is a definite cause of mucosal inflammation, which affects a number of important gastric physiologies such as acid secretion, gastric endocrine function and motility. The chronic persistent nature of infection also results in more dramatic mucosal changes such as atrophy or intestinal metaplasia, the presence of which in the esophagus (Barrett's esophagus) precludes the diagnosis of functional dyspepsia. Since careful endoscopic examination can diagnose reliably H. pylori infection not only in Japan but also in Western contries, it is now feasible and more logical to exclude patients with chronic gastritis caused by H. pylori infection as having dyspeptic symptoms. It is time to establish the Asian consensus to declare that H. pylori infection should be separated from functional dyspepsia.